RT Journal Article
T1 Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice.
A1 Peñasco, Sara
A1 Rico-Barrio, Irantzu
A1 Puente, Nagore
A1 Fontaine, Christine J
A1 Ramos, Almudena
A1 Reguero, Leire
A1 Gerrikagoitia, Inmaculada
A1 Rodriguez-de-Fonseca, Fernando
A1 Suarez, Juan
A1 Barrondo, Sergio
A1 Aretxabala, Xabier
A1 Garcia-Del-Caño, Gontzal
A1 Salles, Joan
A1 Elezgarai, Izaskun
A1 Nahirney, Patrick C
A1 Christie, Brian R
A1 Grandes, Pedro
K1 Organ Culture Techniques
K1 Random Allocation
K1 Receptor, Cannabinoid, CB1
K1 Recognition, Psychology
AB Binge drinking is a significant problem in adolescent populations, and because of the reciprocal interactions between ethanol (EtOH) consumption and the endocannabinoid (eCB) system, we sought to determine if adolescent EtOH intake altered the localization and function of the cannabinoid 1 (CB1) receptors in the adult brain. Adolescent mice were exposed to a 4-day-per week drinking in the dark (DID) procedure for a total of 4 weeks and then tested after a 2-week withdrawal period. Field excitatory postsynaptic potentials (fEPSPs), evoked by medial perforant path (MPP) stimulation in the dentate gyrus molecular layer (DGML), were significantly smaller. Furthermore, unlike control animals, CB1 receptor activation did not depress fEPSPs in the EtOH-exposed animals. We also examined a form of excitatory long-term depression that is dependent on CB1 receptors (eCB-eLTD) and found that it was completely lacking in the animals that consumed EtOH during adolescence. Histological analyses indicated that adolescent EtOH intake significantly reduced the CB1 receptor distribution and proportion of immunopositive excitatory synaptic terminals in the medial DGML. Furthermore, there was decreased binding of [35S]guanosine-5*-O-(3-thiotriphosphate) ([35S] GTPγS) and the guanine nucleotide-binding (G) protein Gαi2 subunit in the EtOH-exposed animals. Associated with this, there was a significant increase in monoacylglycerol lipase (MAGL) mRNA and protein in the hippocampus of EtOH-exposed animals. Conversely, deficits in eCB-eLTD and recognition memory could be rescued by inhibiting MAGL with JZL184. These findings indicate that repeated exposure to EtOH during adolescence leads to long-term deficits in CB1 receptor expression, eCB-eLTD, and reduced recognition memory, but that these functional deficits can be restored by treatments that increase endogenous 2-arachidonoylglycerol.
PB Nature Publishing Group
YR 2019
FD 2019-09-30
LK http://hdl.handle.net/10668/14567
UL http://hdl.handle.net/10668/14567
LA en
NO Peñasco S, Rico-Barrio I, Puente N, Fontaine CJ, Ramos A, Reguero L, et al. Intermittent ethanol exposure during adolescence impairs cannabinoid type 1 receptor-dependent long-term depression and recognition memory in adult mice. Neuropsychopharmacology. 2020 Jan;45(2):309-318
DS RISalud
RD Apr 19, 2025